• Marina Boccardi, Martina Bocchetta, Félix C Morency, D Louis Collins, Masami Nishikawa, Rossana Ganzola, Michel J Grothe, Dominik Wolf, Alberto Redolfi, Michela Pievani, Luigi Antelmi, Andreas Fellgiebel, Hiroshi Matsuda, Stefan Teipel, Simon Duchesne, Clifford R Jack, Giovanni B Frisoni, and EADC-ADNI Working Group on The Harmonized Protocol for Manual Hippocampal Segmentation and for the Alzheimer's Disease Neuroimaging Initiative.
• LENITEM (Laboratory of Epidemiology, Neuroimaging and Telemedicine) IRCCS - Centro S. Giovanni di Dio - Fatebenefratelli, Brescia, Italy. Electronic address: mboccardifbf@gmail.com.
• Alzheimers Dement. 2015 Feb 1;11(2):175-83.

BackgroundThe European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms.MethodsSixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction.ResultsHippocampal volumes (mm(3)) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = <-0.468, P = <.0005). Cerebrospinal fluid spaces (mm(3)) were as follows: controls: left = 23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11 (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy.ConclusionsThis work provides reference hippocampal labels for the training and certification of automated segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol.Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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